Male Sprague—Dawley rats were subjected to unilateral nephroadrenalectomy and received 1% NaCl as their drinking water. To induce hypertension, the remaining adrenal was enucleated in half the number of rats used. Sixty days following surgery the rats bearing regenerating adrenals had significantly elevated systolic blood pressures with associated cardiac and renal enlargement. At this time isolated adrenal cells were prepared and the effects of ACTH on corticosteroidogenesis were studied. Plasma and adrenal cell levels of 11–deoxycorticosterone (DOC) were measured by radioimmunoassay and corticosterone and 18–hydroxydeoxycorticosterone (180H–D0C) were assayed spectrophotometrically. Initial stimulation of DOC, corticosterone and 180H–D0C production in adrenal cells from adrenal— regenerating rats required larger doses of ACTH than in control cells from normal rats. Furthermore, the magnitude of DOC and corticosterone production, even at doses of ACTH exceeding threshold levels, was depressed in cell suspensions from regenerated adrenals, while 180H–D0C levels were similar to control values. The concentration of DOC in peripheral plasma of adrenal—regenerating rats was subnormal, while the plasma 18OH–DOC/corticosterone ratio was increased due to enhanced levels of 180H–D0C. Although adrenal regeneration is believed completed 6–8 weeks following enucleation, the gland remains hypofunctional. The increased 18OHDOC/ corticosterone ratio in peripheral plasma and adrenal cells from adrenal—regenerating rats may be an important factor in the persistence of elevated blood pressure. (Endocrinology92: 174, 1973)